AU3780000A - Compositions for stabilizing oxygen-labile species - Google Patents
Compositions for stabilizing oxygen-labile species Download PDFInfo
- Publication number
- AU3780000A AU3780000A AU37800/00A AU3780000A AU3780000A AU 3780000 A AU3780000 A AU 3780000A AU 37800/00 A AU37800/00 A AU 37800/00A AU 3780000 A AU3780000 A AU 3780000A AU 3780000 A AU3780000 A AU 3780000A
- Authority
- AU
- Australia
- Prior art keywords
- compositions
- soluble
- compositions according
- water
- oxygen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/30—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing heterocyclic ring with at least one nitrogen atom as ring member
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/23—Sulfur; Selenium; Tellurium; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
- A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/678—Tocopherol, i.e. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/28—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing nitrogen, oxygen and sulfur
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Dermatology (AREA)
- Gerontology & Geriatric Medicine (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cosmetics (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
Abstract
This invention relates to compositions and methods for stabilizing oxygen-labile species. More particularly, it relates to compositions containing one or more oil- and/or water-soluble oxygen-labile species and one or more stabilizing elements. It also relates to methods of making such compositions and methods of using such compositions.
Description
-1-
AUSTRALIA
PATENTS ACT 1990 COMPLETE SPECIFICATION FOR A STANDARD PATENT
ORIGINAL
a
C,
C
a a.
Name of Applicant/s: Actual Inventor/s: Address for Service: Invention Title: Johnson Johnson Consumer Companies, Inc.
John Kung and Jue-Chen Liu BALDWIN SHELSTON WATERS MARGARET STREET SYDNEY NSW 2000 'COMPOSITIONS FOR STABILIZING OXYGEN-LABILE SPECIES' The following statement is a full description of this invention, including the best method of performing it known to me/us:- File: 28203AUP00 I I la COMPOSITIONS FOR STABILIZING OXYGEN-LABILE SPECIES Reference to copending patent applications: This patent application is being filed simultaneously with U.S. Patent Application Serial No. (Attorney Docket No. NEU- 017; inventors Christopher Stahl and Frederick Woodin) and hereby incorporates herein s the disclosure of such patent application by reference.
Field of the Invention This invention relates to compositions and methods for stabilizing oxygen-labile species in compositions. More particularly, it relates to compositions containing one or 10 more oil- and/or water-soluble oxygen-labile species and one or more stabilizing elements. It also relates to methods of making such compositions and methods of using such compositions.
Background of the Invention 1s For many years, it has proven difficult to make stable compositions containing oxygen-labile species. "Oxygen-labile" species are those that are easily oxidized and readily decompose when exposed to the environment. Such oxygen-labile species are, therefore, very difficult to formulate into compositions in combination with other compounds that may accelerate such decomposition or that may be exposed to the environment over time.
In recent years, it has become desirable, for example, to include various vitamin compounds in topical skin care compositions in order to nourish or repair the skin.
However, those of ordinary skill in the art have found that these vitamin compounds are quite unstable in topical compounds due to the fact that they are easily oxidized and decompose quickly, resulting in loss of efficacy and discoloration of the composition.
2 5 Thio compounds such as metabisulfite and sulfite compounds have been known as good water-soluble antioxidants and have been added to compositions to prevent such oxidation problems. However, these compounds may cause sensitization in certain individuals and are not useful for administration to humans. They also possess noxious odors and are unpleasant to use. Japanese Patent Publication No. 53-7488, for example, 2 -2suggests that combining ascorbic acid with dl-N-acetyl homocysteine thiolactone or Nacetyl-L-cysteine and sulfite in an aqueous solution of ascorbic acid results in a composition that can be stored stably over a long period.
EP 0 349 797 B1 mentions the combination of N-acetykcysteine and ascorbic acid or ascorbate as a stabilizer for the N-acetylcysteine. Slovakian publication, Farm. Obzor LIV 1985 p. 513 (Pharmacology Review) mentions the combination of N-acetylcysteine and ascorbic acid at a pH of 6.2. Both N-acetylcysteine and ascorbic acid are watersoluble. However, none of these references indicate that N-acetylcysteine would serve to stabilize an oil-soluble oxygen-labile species.
10 Thus, it is an object of this invention to provide compositions that contain oxygen-labile species that are stable over long periods of time.
It is another object of this invention to provide compositions that contain oilsoluble and/or water-soluble oxygen-labile species that are stable over long periods of time.
Yet another object of this invention is to provide compositions that contain both "oil-soluble and water-soluble oxygen-labile species that are stable over long periods of time.
It is another object of this invention to provide methods of making stable compositions containing oxygen-labile species.
2 0 Another object of this invention is to provide methods of using the stable oxygenlabile species-containing compositions of this invention.
Yet another object of this invention is to provide skin care compositions that contain oxygen-labile species such as vitamins and their derivatives for topical use on the skin.
Summary of the Invention We have discovered that certain oil-soluble and/or water-soluble oxygen-labile species may be stabilized in compositions by the addition of one or more stabilizer compounds. Such stabilizer compounds are selected from the following categories:
I
-3 a) thio-containing compounds, such as sulfites and cysteine derivatives; and b) glycoproteins, such as lactoferrin.
Oil-soluble oxygen-labile species may include vitamin compounds such as retinoids, choleciferol, vitamin K, tocotrienol and tocopherol derivatives, essential fatty acids and the like. Water-soluble oxygen-labile species may include vitamin compounds such as ascorbic acid and its derivatives, niacin, thiamine, riboflavin, folic acid, pyrodoxine, pantothenic Sa. acid, niacinamide, lipoic acid, dihydrolipoic acid, essential amino acds and the like. The oil-soluble oxygen-labile species may be present in the compositions of this invention in amounts of from about 0.01 to about 10%. The water-soluble oxygen-labile species may i** 10 be present in the compositions of this invention in amounts of from about 0.01 to about Detailed Description of the Preferred Embodiments The compositions of this invention contain certain oil-soluble and/or watersoluble oxygen-labile species which are stabilized in compositions by the addition of one 1s or more stabilizer compounds. Such stabilizer compounds are selected from the following categories: a) thio-containing compounds, such as sulfites and cysteine derivatives; and b) glycoproteins, such as lactoferrin.
The stabilizers which are induded in the term "thio-containing compounds" include such compounds as sulfites and metabisulfites, cysteine derivatives and glutathione. More preferably, the thio-containing compounds are cysteine derivatives. Most preferably, the thio-containing compound is N-acetylcysteine. Thio-containing compounds are wellknown as stabilizers of water-soluble compounds as they reside in the water phase of compositions. However, they are not known to be capable of stabilizing oil-soluble 2 5 compounds as they do not reside in the oil phase of compositions. Surprisingly, we have found that compositions containing both water- and oil-soluble oxygen labile species as well as thio-containing compounds are stable over long periods of time. Preferably, the amount of thio-containing compound should range from about 0.001 to about 5% of the 4 weight of the composition. More preferably, there should be from about 0.01 to about of the composition by weight.
Furthermore, compositions containing oil-soluble and/or water-soluble oxygen labile species and stabilizer compounds, selected from the group of glycoproteins are surprisingly stable. The glycoproteins that are useful in the compositions of this invention include lactoferrin and the like. Unexpectedly, such glycoproteins, large molecules that reside in the water phase of compositions, and which are known to be biologically active ~have proven to be viable as stabilizer compounds in the compositions of this invention.
Although it is unknown how these proteins serve to stabilize the compositions of this 10 invention, it is theorized that the proteins may reside at the oil/water interface of the compositions of this invention and are therefore active in both phases. Alternatively, the proteins may somehow adsorb or attract the ions that would otherwise cause oxidation of the oxygen-labile species of the compositions of this invention. Preferably, the amount of glycoprotein compound should range from about 0.00001 to about 5% of the weight of is the composition. More preferably, there should be from about 0.01 to about 1% of the composition by weight.
Most preferably, the glycoprotein useful in the compositions of this invention is lactoferrin, a milk-derived protein that chelates iron and has a molecular weight of 80,000 daltons. Although lactoferrin is known as an anti-free radical compound in biological 2 0 systems, it has heretofore been unknown for use in formulations. Whether an antioxidant or chelator which is active in a biological system will be active in a composition is completely unpredictable.
The oxygen-labile species may exist in the compositions of this invention either individually or as a combination. For example, vitamins A, C or E may be present in the 2 5 compositions of this invention individually, one of such vitamins in one composition.
Alternatively, various combinations of vitamins may be present within an individual composition, for example, vitamin C (ascorbic acid) may be present in a composition with either thio-containing compounds, such as sulfites and cysteine derivatives or a glycoprotein, such as lactoferrin or both. Vitamins A and C may be present within an 5 individual composition with thio-containing compounds, such as sulfites and cysteine derivatives or a glycoprotein, such as lactoferrin or both to achieve a stable formulation.
Vitamins C and E may be present within an individual composition with thio-containing compounds, such as sulfites and cysteine derivatives or a glycoprotein, such as lactoferrin or both. Vitamins A, C and E may also be present in an individual composition with thiocontaining compounds or a glycoprotein or both. Surprisingly, in each of these compositions, both the water-soluble and oil-soluble oxygen-labile species are stable over a long period of time. One of ordinary skill in the art would expect that vitamins A and C together would not be stable as Vitamin C tends to sacrifice itself to stabilize Vitamin A.
10 Compositions of this invention containing both Vitamins A and E together, we have found, preferably contain at least about 0.0001% of Vitamin C for ensuring stability of all materials.
The compositions of this invention may be utilized in dosage forms suitable for cosmetic or pharmaceutical use. For example, the compositions of this invention may be made in the forms of emulsions, creams, lotions, gels, essences, milks, toners, hydroalcoholic solutions, multivesicular systems, suspensions, patches, masks, sticks, and other dosage forms suitable for therapeutic use, including oral administration forms.
The compositions of this invention may be made using conventional formulation :technology. For example, in a standard oil-in-water emulsion, the starting water phase should be purged with either nitrogen or argon to displace any residual oxygen.
Alternatively, the water phase may be heated to 80 0 C and held at that temperature at least about ten minutes to reduce oxygen solubility. A conventional oil phase should be made and the oil phase poured into the water phase. After phasing, the formulation should be blanketed with an inert gas such as nitrogen or argon and the formulation permitted to cool to room temperature. As the temperature reaches 450 C, the stabilizer compound should be added to the formulation. The stabilizer compound should be mixed into the formulation for about ten minutes, after which the oxygen-labile species may be introduced into the formulation. Neutralization to the appropriate pH may be made prior to or subsequent to the addition of the oxygen-labile species, depending upon the oxygen- -6 labile species utilized. For example, neutralization is preferred subsequent to adding ascorbic acid, but should be accomplished prior to adding retinol. The formulation resulting from this process should be packaged in an oxygen-impermeable package, such as an aluminum tube.
The pH of the formulations of this invention is preferably in a range that is suitable for a particular oxygen-labile species used in the compositions. The pH should reflect as closely as possible the physiological pH of the skin without compromising the chemical stability of the oxygen-labile species. For example, the preferred pH e. environment for ascorbic acid should about 5.5 and above. The preferred pH for retinol 10 should be about 5.5 and above. Preferably, the pH should be between about 5.5 and about 9. pH greater than about 10 may result in irritation to the skin when applied topically.
During manufacture of the compositions of this invention, oxygen exposure should be minimized as much as possible so as to reduce the possibility of oxidizing the is oxygen-labile species and preserve its stability. Therefore, to the extent possible, all oxygen in the manufacturing system should be displaced with nitrogen or argon gas, as set forth, for example, in U.S. Patent No. 5,559,149.
The compositions of this invention may be used in therapeutic situations wherever the oxygen-labile ingredients are therapeutically active. For example, ascorbic acid can be used for collagen synthesis, elastin synthesis or skin depigmentation and other known uses. Tocopherol, for example, may be useful in free radical scavenging internally or topically. The compositions of this invention may be applied topically to the skin on a daily or more or less frequent basis. The compositions of this invention deliver therapeutic quantities of oxygen-labile species to the skin.
Other emollients and surface active agents have been incorporated in the emulsions, including glycerol trioleate, acetylated sucrose distearate, sorbitan trioleate, polyoxyethylene monostearate, glycerol monooleate, sucrose distearate, polyethylene glycol (50) monostearate, octylphenoxypoly (ethyleneoxy) ethanol, -7 decaglycerin penta-isostearate, sorbitan sesquioleate, hydroxylated lanolin, lanolin, triglyceryl diisostearate, polyoxyethylene oleyl ether, calcium stearoyl-2lactylate, methyl glucoside sesquistearate, sorbitan monopalmitate, methoxy polyethylene glycol-22/dodecyl glycol copolymer (Elfacos E200), polyethylene glycol-45/dodecyl glycol copolymer (Elfacos ST9), polyethylene glycol 400 distearate, and lanolin derived sterol extracts, glycol stearate and glycerol stearate; alcohols, such as cetyl alcohol and lanolin alcohol; myristates, such as isopropyl myristate; cetyl palmitate; cholesterol; stearic acid; propylene glycol; glycerine, sorbitol and the like.
10 The composition of this invention can contain additives, as required, such as a humectant, an antioxidant, a preservative, a flavor, fragrances, a surface active agent, a binder, and the like, as well as skin protectant agents, therapeutic agents and "cosmeceuticals".
Examples of the preservatives include salicylic acid, chlorhexidine .15 hydrochloride, phenoxyethanol, sodium benzoate, methyl para-hydroxybenzoate, ethyl para-hydroxybenzoate, propyl para-hydroxybenzoate, butyl parahydroxybenzoate and the like.
Examples of the flavor and fragrance include menthol, anethole, carvone, eugenol, limonene, ocimene, n-decylalcohol, citronellol, a-terpineol, methyl salicylate, methyl acetate, citronellyl acetate, cineole, linalool, ethyl linalool, vanillin, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon leaf oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil and the like.
Examples of surface active agents include sodium alkyl sulfates, sodium lauryl sulfate and sodium myristyl sulfate, sodium N-acyl sarcosinates, sodium N-lauroyl sarcosinate and sodium N-myristoyl sarcosinate, sodium dodecylbenzenesulfonate, sodium hydrogenated coconut fatty acid monoglyceride sulfate, sodium lauryl sulfoacetate and N-acyl glutamates, N-palmitoyl -8 glutamate, N-methylacyltaurin sodium salt, N-methylacylalanine sodium salt, sodium a-olefin sulfonate and sodium dioctylsulfosuccinate; N-alkylaminoglycerols, N-lauryldiaminoethylglycerol and N-myristyldiaminoethylglycerol, N-alkyl-Ncarboxymethylammonium betaine and sodium 2-alkyl-l-hydroxyethylimidazoline betaine; polyoxyethylenealkyl ether, polyoxyethylenealkylaryl ether, polyoxyethylenelanolin alcohol, polyoxyethyleneglyceryl monoaliphatic acid ester, polyoxyethylenesorbitol aliphatic acid ester, polyoxyethylene aliphatic acid ester, higher aliphatic acid glycerol ester, sorbitan aliphatic acid ester, Pluronic type surface active agent, and polyoxyethylenesorbitan aliphatic acid esters such as i 10 polyoxyethylenesorbitan monooleate and polyoxyethylenesorbitan monolaurate.
Emulsifier-type surfactants known to those of skill in the art should be used in the compositions of this invention.
Examples of the binder or thickener include cellulose derivatives such as alkali metal salts of carboxymethylcellulose, methyl cellulose, hydroxyethyl 15 cellulose and sodium carboxymethylhydroxyethyl cellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, gums such as carrageenan, xanthan gum, tragacanth gum, caraya gum and gum arabic, and synthetic binders such as polyvinyl alcohol, polysodium acrylate and polyvinyl pyrrolidone.
Thickeners such as natural gums and synthetic polymers, as well as preservatives such as methylparaben, butyl paraben, propylparaben and phenoxyethanol, coloring agents and fragrances also are commonly included in such compositions.
Other active ingredients such as sunscreen materials and antimicrobial materials may be utilized in the compositions of the present invention provided that they are physically and chemically compatible with the other components of the compositions. For example, moisturizing agents such as propylene glycol, allantoin, acetamine MEA, oat protein and hyaluronic acid and other humectants may be added to the retinoid-containing formulations of this invention in order to provide 9 moisturizing activity in conjunction with the retinoid-related activity of the products.
Other proteins and amino acids may also be incorporated. Sunscreens may include organic or inorganic sunscreens, such as octylmethoxycinnamate and other cinnamate compounds, titanium dioxide and zinc oxide and the like.
Other ingredients may include agents which assist in protecting the skin from aging, such as sunscreens, anti-oxidant vitamins such as ascorbic acid, vitamin B, biotin, pantothenic acid, vitamin D, vitamin E and vitamin C. Yeast extract, gingko biloba, bisabolol, panthenol, alpha hydroxy acids and oligosaccharides such as melibiose are among other ingredients which assist in preventing aging of the skin 10 by such means as irritation mitigation, oxidation mitigation, healing, affecting S° retinoid metabolism and inhibiting the production of elastase.
Skin color evening ingredients and depigmentation agents may also be ~effective in the products of this invention. Such ingredients may include hydroquinone, licorice extract, kojic acid, gatuline A (pilewort extract), micromerol 15 (butylene glycol and apple extract), glutathione, arbutin, placenta extract, ascorbic acid, magnesium-L-ascorbyl-2-phosphate and the like.
Compositions which assist in the reduction of lines and wrinkles may also be added to the compositions of this invention. For example, alpha hydroxy acids, hyaluronic acid, Gatuline R (fagus silvitica extract), pigments and scattering aids such as mica, zinc oxide and titanium dioxide may be used in the compositions of this invention in this capacity. Various natural extracts such as tannins, flavenoids, saponins and the like may also be added.
Anti-inflammatory agents may also be used in the compositions of this invention. Not only should these agents assist in mitigating irritation, they may assist the retinoids in treating wrinkles and lines in the skin. Steroidal antiinflammatory agents, including but not limited to, corticosteroids such as hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionate, clobetasol valerate, 10 desonide, desoxycorticosterone acetate, dexamethasone, dichlorisone, deflorasonediacetate, diflucortolone valerate, fluadronolone, fluclarolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocionide, flucortine butylester, fluocortolone, flupredidene (flupredylidene) acetate, s. s flurandronolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate, fluradrenalone acetonide, medrysone, amciafel, amcinafide, betamethasone and its esters, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, triamcinolone and mixtures thereof may be used. Preferably, hydrocortisone may be used.
Nonsteroidal anti-inflammatory agents may also be employed in the compositions of this invention, such as salicylates (including alkyl and aryl esters of salicylic acid), acetic acid derivatives (including arylacetic acid and its derivatives), fenamates, propionic acid derivatives and pyrazoles or mixtures thereof. Other synthetic and natural anti-inflammatory agents may also be used.
Additional active ingredients having topical activity may be utilized in the compositions of this invention. Azole-type anti-fungal and anti-bacterial agents may be employed in the compositions of this invention in their base form. For example, ketoconazole, miconazole, itraconazole, metronidazole, elubiol, and like related imidazole antifungals and antibacterials are useful in the topical formulations of this 2 5 invention.
The advantages of the invention and specific embodiments of the skin care compositions prepared in accordance with the present invention are illustrated by the following examples. It will be understood, however, that the invention is not 4., 11 confined to the specific limitations set forth in the individual examples, but rather to the scope of the appended claims.
Example 1: An Emulsion containing A Hydrophilic Oxygen-Labile Species (Ascorbic Acid) A composition in accordance with this invention was made by combining the following o.ingredients in a water phase: Ingredients w/w Water q.s. to 100% Disodium EDTA 0.10% Glycerin 5.00% Phenoxyethanol 0.73% Methylparaben 0.20% Propylparaben 0.07% Hydroxyethyl cellulose 0.3% Xanthan Gum 0.50% A batch of 1 kilogram was made according to the following process. The weight of the beaker was recorded, and the water then added. Because this process requires boiling, an additional 50 grams of water was added to the beaker to counter the effect of evaporation.
The beaker was covered with aluminum foil and beginning boiling the water. The water was permitted to boil for at least five minutes. The heat was turned off, and the water cooled to 80 0 C. The water phase was kept heated at least for ten minutes. The disodium EDTA was added and the water phase mixed until the EDTA was fully dissolved and clear. The xanthan gum and hydroxyethyl cellulose were slurried into the glycerin in a side 2 5 container. The slurry was poured into the water phase. Tthe preservatives were added the phenoxyethanol, methyl paraben and propyl paraben). The water phase was held at 800.
Separately, in another container, an oil phase was created using the following ingredients: 12 Ingredients w/w Butyl hyroxytoluene 0.10% Glyceryl monostearate Peg-100 stearate 5.00% Cetyl palmitate 1.00% s Cetyl alcohol 1.00% C12-15 alkyl benzoate 4.00% White petrolatum 1.50% Butyl Methoxydibenzoyl methane 1.00% :'."Octyl methoxycinnamate 7.50% Aall of the above named oil phase ingredients were combined in a beaker, and heated to 80 0 C. The oil phase was mixed homogeneously. When both phases were at 80 0 C, the oil was phased into the water phase. The batch was cooled to room temperature. When at 45 0 C, the post-additions were added to the batch.
Ingredients %w/w Ascorbic acid 5.00% N-acetyl cysteine 0.10% Ethanol 2.78% NaOH q.s. to desired pH.
2 0 The stabilizing compound, in this case the N-acetyl cysteine was added first, and allowed to mix for at least ten minutes. After the requisite mixing, the ascorbic acid was added.
The sodium hydroxide was then added to neutralize the batch. The mixer speed was slowed down when the neutralization solution was added to minimize any whipping of air into the beaker. Finally, the ethanol was added and water added to the batch q.s. The product was filled in aluminum tubes. The compositions may also be placed in any other suitable oxygen impermeable package.
13 Example 2: Another composition according to this invention was made including both 2% Vitamin C and 0.1% N-acetyl cysteine. The composition induded the following ingredients and was made in accordance with the method set forth in Example 1: S. S Chemical Name wt/wt Water Phase Water 60.72% Disodium EDTA 0.10% Glycerin 5.00% Phenoxyethanol 0.73% Methyl paraben 0.20% Propyl paraben 0.07% Hydroxyethylcelluose 0.30% Xanthan Gum 0.50% Oil Phase Butylated hydroxytoluene 0.10% Octyl methoxycinnamate 7.50% Butyl methoxydibenzoyimethane 1.00% Glyceryl Stearate (and) PEG- 100 5.00% Stearate Cetyl Palinitate 1.00% Cetyl Alcohol 1.00% Steari Alcohol 0.50% C2. is Alkyl Benizoate 4.00% White Petrolau 1.50% Post additions Ascorbic acid 5.00% ri-acetyl cysteine 0.10% Ethanol 2.78% NaOH 2.90% Another formulation may also be made in accordance with this Example 2, however the 0.1%.N-acetyl-cysteie may be replaced with 1% lactoferrin or inifemrn..
14 Example 3: The following is another formulation that may be made in accordance with this invention, containing ubiquinone, an anti-oxidlant. The following formulation may be made in accordance with the procedure set forth in Example 1.
**.Chemical Name wt/wt Water Nham Water 64.62% Disodiurn EDTA 0.10% Dex Panthenol 1.00% Preservatives 0.
73 carbomner 0.35% Glyceryl Monostearate PEG-100 Stearate 5.00% Caprylic/Capric Tnglycerides 3.00% Cetyl Alcohol 2.00% Octyl hydroxystearate 2.00% :C1201 CiAlkyl Benzoate 4.00% methoxydibenzoyimethane 3.00% *Octyl methoxycinnaae 7.50% Post.- Addiuiots Ubiquinone 0.10% Lactoferrin (and) Thioxanthine (and) Uric Acid 0.50% 1.50% NaOH (109/) 4.60% 100.00% *adjust NaOH concentration to desired pH This formulation should be stable over a period of time and under exposure to heat.
Example 4: The following is another formulation that may be made in accordance with this invention, containing ascorbyl palmitate, an anti-oxidlant. The following formulation may be made in accordance with the procedure set forth in Example 1.
Chemnical Name t/vt WaterMhas Water 64.62% DisodiurnEDTA0.0 Glycerin 3 S0% Xanthan Gum 0.so0% 15 Magnesium Aluminumn Silicate 1.00% Preservatives 1 .00% O Aa Cetearyl Glucoside 3.00% Stearyl Alcohol 1.-50% Cetyl Alcohol 1. Octyl hydroxystearate 2 .00% C12-15 AlW Benzoate 4 .00% Dirnethicone 1.00% Ascorbyl PaLmitate 0.50% Octyl methoxycininamate 4 .00% Post adtk .N-acetyl cysteine 0.01w Green Tea Extract 15 Chamnomile Extract *NaOH 4 Example The following is another formulation that may be made in accordance with this invention, :containing hydroquinone, a skin-bleaching agent. The following formulation may be made in accordance with the procedure set forth in Example 1.
Chemical Namne wt/wt *25 Waz.er MuSe o:Water 75.32% Propylene Glycol 2.00% Dex Panthenol 1.00% Preservatives 0.73% carbomner 0.3 Od Tba Glyceiyl Monostearate PEG-100 Stearate 5.00% Mineral Oil 4.00% Stearic Acid 2.00% Petrolatum 1.00% Post Addziias Hydroquinone 2.00% Lactoferrin (and) Thioxanthine (and) Uric Acid 2.00% NaOH 4.60% 100.00% adjust NaOH concentration to desired pH
S
9 9 9 15 Example 6: The stability of different formulations containing retinol, ascorbic acid and/or tocopherol as set forth in Examples 7 and 8 below were monitored in terms of appearance and HPLC assay. The degraded products of retinol, ascorbic acid or tocopherol are yellow or brownish in color. The freshly prepared samples were white creams. Discoloration to yellow or brown indicates the instability.
Effect of 1% Iniferine on Retinal, Ascorbic acid and Tocopherol stabilitv (no BHT, no EDTA) Example Active Assay (4C, Color 4 weeks) fAssay (40C, 4 Color (40*C, 4 weeks) veks I weeks) Example 7 Retinol 1 0.168 1 White (no discoloration) 1 0.122 Yellowish (discolored) Ascorbic acd1 4.8 -F 4.68 (97.5%) Exampe 8 etiol 1 0.974 e n icooin 0.65 94.84% Wie(odsooan :Example oheriol 0.954 V____(nodiscoloration)[0.6 V_____((nndscoloration Ascorbic acid 1 4.81 (96.5%) Tocphco 101 1 0.98 (97.0 If ascorbic acid is removed from the formulations, as set forth below, the formulations are not as stable, even with additional BHT and EDTA. However, formulations containing ascorbic acid and tocopherol were found to be stable. Thus, ascorbic acid assists in stabilizing tocopherol.
Effect of 5% Ascorbic acid on Retinal and Tocopherol stability Example active Target value 25* 0 C, 1 week Color Example 9 Retinal 0.1725 0.1695 White no discloraion) Ascorbic Adid 5.00 4.96 Tocopherol 1.00 0.96 Example 10 Rernol 0.1725 0.15 Brigh ellow discolored ITocopherol 1.00 0.89 Due to the irnmediate loss of retinol and tocopherol and significant discoloration, no further stability was conducted on Example 10. The addition of N-acetylcysteine slightly enhances the stability of retinol and tocopherol.
17 Effect of Ascorbic concentration on Ascorbic acid, Retinol and Tocopherol Stability (compositions referred to in Example 9) Initial Ascorbic active 8 weeks 4-C 8 weeks concentration 0.10 Retinol 0.1655 (100/6) 0.1600 (96.7%) Ascorbic Acid 0.05 0.04 Tocopherol 0.98 (100%) 1.00 (100%) 1% Retinal 0.1582 (1000%) 0.1603 (100%) Ascorbic Acid 0.89 (100%) 0.80 (89.9%) Tocopherol 0.99 (1000%) 0.99 (100%) Retinol 0.1657 (100%) 0.1664 (100) Ascorbic acid 9.80 (100%) 9.90 (100%) Tocopherol 1.10 (100%) 1.12 (100%) If we refer to the stability of the compositions at 8 weeks at 40 0 C as the initial, all A (retinol), C (ascorbic acid), E (tocopherol) samples are stable. The data also suggests that it is important to control the manufacturing process for low concentration ascorbic acid to minimize any loss in stability.
Example 7: A formulation according to this invention was made containing Vitamins A, C, E and iniferine. It did not include BHT, an antioxidlant or disodiumn EDTA, a chelating agent.
Chemical Name wt/wt Water M~ Water 65.1'5% Disodiumn EDTA 0.00% Glycerin 5.00% Preservative 0.73% Preservative 0.3 Preservative 0.17% Hydroxyethylcelltilose 0.30% Xanthan Gum 0.50% Od Pis Butyffhydroxytoluene 0.00% Glyceryl Monostearate PEG- 100 5.00% Cetyi PAlnitate 1.00% Ceryl Alcohol 1.00% Stearyl Alcohol 0.50% Benzoate 4.00% White Petrolatum 1.50% Pst Additi 18 Ascorbic Acid 5.00% Tocopherol 1.00% Retinol 0.40% Lactoferrin; thioxanthine; uric acid 0.00% Ethanol 2.78% NaOH 5.62% Example 8: A formulation according to this invention was made containing Vitamins A, C, E and iniferine. It included BHT, an antioxidant and disodiumn EDTA4, a chelating agent.
*Chemical Name wt/wt WaTer Pbar Water 64.15% Disodium EDTA 0.00% Glycerin 5.00% Phenoxyethanol 0.73% Methyl paraben 0.35% *20 Propyl paraben 0.17% Hydroxyethylceluidose 0.30% *Xanthan Gum 0.50% Od AUX Butyihydroxytoluene 0.00% 25 Glyceryl Monostearate PEG- 100 5.00% etyl Palmitate 1.00% Cetyl Alcohol 1.00% Stearyl Alcohol 0.50% C,.c, 5 Alky Benzoate 4.00% White Petrolatum 1.50% IPost Additirns Ascorbic Acid 5.00% Tocopherol 1.00% Retinol 0.40% Lactoferrin; thioxanthine; uric acid 1.00% Ethanol 2.78% NaOH 5.62% Example 9: Another formulation according to this invention was made containing Vitamins A, C and E but did not include sunscreens. The composition was made in accordance with the procedure set forth in Example 1.1 19 Chemical Name wt/wt Wazer P1%"s Water 63.95%/ Disodiumn EDTA 0.10% Glycerin 5.00% Phenoxyethanol 0.73% Methyl paraben 0.35% Propyl paraben 0.17% Hydroxyethylcellulose 0.30% Xanthan Gum 0.50% Oil Phase Butylhdroxytoluene 0.10% Glyceryl Monostearate PEG-too0 .5.00% Cetyl Palmi tate 1.00%/ *Cetyl Alcohol 1.00% Stearyl Alcohol 0.50% Alkyl Benizoate 4.00% White Petrolatum 1.50% Post -A ddrikz Ascorbic Acid 5.00% Tocopherol 1.00% :Retinol 0.40% Lactoferrin; thioxanthmne; uric acid 1.00% Ethanol 2.78% NaOH 5.62% ~30 Another 3 formulations containing 0. 1% 1 and 10% ascorbic acid respectively were made in accordance with example 9, however, 1% lactoferin/thioxanthine/uric acid was replaced with 1% lactoferrin.
Example Yet another formulation. was made in accordance with the method set forth in Example 1.
This composition contained Vitamins A and E and inifenine.
Chemical Name wt/wt Water 68.95% Disodium EDTA 0.10% Glycerin 5.00% Phenoxrethanol 0.73% Methyl paraben 0.35% Propyl paraben 0.17% Hydroxyethyicelltdose 0.30% Xanthan Gum 0.50% Butylhydroxytoluene 0.100/ Glyceryl Monostearate PEG. 100 5.00% Cetyl Palmitate 1.00% Cetyl Alcohol 1.00% Stearyl Alcohol 0.50% C1 2 CIs Alkyl Benzoate 4.00% White Petrolatum 1.50% Tocopherol -1.00% Retinol 0.40% Lactoferrin; thioxanthine; uric acid 1.00% Ethanol 2.78% NaOH (20%1) 5.62% ::::*Example 11: A formulation containing Chemical Namne wt/wt Water Pbaw Water 52.85% Disodiurn EDTA 0.10% .:Glycerin 5.00% Phenoxyethanol 0.73% Methyl paraben 0.3 Propyl paraben 0.17% Hydroxyethylcelluilose 0.30% Xanthan Gum 0.50% Od Pus Butylhydroxytoluene 0.10% Octyl methoxydnnamate Avobenzone 3.00% Glyceryl Monostearate PEG- 100 5.00% Cetyl PArnirae 1.00% Cetyl.Alcohol 1.00% Stearyl Alcohol 0.50% Alkyl Benzoate White Petrolatum 1.50% Jbst Addiicns Ascorbic Acid 5.00% Tocopheral 1.00% Polysorbate 20 1.00% Lactoferrin, thioxanthine, uric acid 1.00% j 21.
Ethanol 2.78% NaOH (20%b) 5.620/ Example 12: A composition was made in accordance with this invention contai ning Vitamrins A and C with Iniferine alone without N-acetyl cysteine. After 13 weeks exposure to 40'C, of the Vitamin C was retained and there was no loss in A.
Chemical Name wt/wt Water Phase Water 73.96% Disodiumn EDTA 0.20% Phenoxyethanol 0.73% *Methyl paraben 0.20% Propyl paraben 0.07% 1.00% Oil Phase Burylhydroxytoluene 0.10% GMS 2.00% Getearyi Glucoside 3.00% C12-15 alkyl benzoate 2.00% Avobenzone 2.00% *Octyl methoxycinnamate 4.00% Palmnitate 0.50% Post Additions ascorbic acid 2.00% n-acetyl cysteine 0.00% Retinol 50c 0.27% unc acid 1.00% isaparaffin; laureth-7; polyacrylarnide 1.50% NaOH 5.47% Example 13: The-following composition contained only Vitamin C with N-acetyl cysteine. It was made in accordance with the procedure set forth in Example 1 except that the composition was bodled rather than purged with inert gas to remove oxygen.
Chemical Name wt/wt WaterPhase Waer 64.92% Disodium EDTA 0.10% -22 Glycerin 5.00% Phenoxyethanol 0.73%/ Methyl paraben 0.20% Propyl paraberi 0.07%/ Hydroxyethylcellulose 0.30% Xanthan Gum 0.50%/ Od RM" *Butylhydroxytoluene 0.10% Glyceryl Monostearate Cetyl Alcohol 1.00% Stearyl Alcohol 0.50% *C12-C15 Alkyl Benzoate 4.00% White Petrolatum 1.50% *Avobenzone 1.00% Octyl methoxycinnamate 7.50% lbt -Addiics .00/ Ascorbic ethanol 2.78% n-Acetyl Cysteine 0.10% NaOH 1.70% After exposure to 50 0 C for 13 weeks, 96% of the Vitamin C remained in this composition.
.:Example 14: A composition in accordance with this invention was made using the procedure set forth in Example 1. This composition contained Vitamins A and C as well as Iniferine and N-acetyl cysteine. After 13 weeks incubation at 40'C, 90% C and 96% A remained in the composition.
Chemnical Name wt/wt Water 51.27% Disodium EDTA 0.10% Glycerin 5.00% Phenoxyethanol 0.73% Me*hy paraben 0.35% Propyl paraben 0.17% Hydroxyethycellulose 0.15% Xanthan Gum 0.50% Burfiltydroxytoluene 0.10% I 1 0 1 23- Ocry methoxyciriamate 7.50% Avobenzone 3.00% Glyceryl Monostearate PEG-lao Stearare 5.00% Wey Palrnitate 1.00% Cetyl Alcohol 1.00% Stearyl Alcohol 0.50%/ C12-C15 Alkyl Benzoares 4.00% White Petrolatum 1.5O 0 Pabst- Aadiiti Ascorbic Acid 5.00% Tocopherol 0.05% Retinol 0.25% Lactoferrin; thioxanthine; uric acid 1.00% n-acetyl cysteine 0.0 1% Ethanol 2.78% *NaOH 9.04% Example A composition in accordance with this invention was made using the procedure set *~.forth in Example 1. This composition contained Vitamins A, C and E as well as Iniferine and N-acetyl cysteine. After 11.5 weeks incubation at 401C, 92% of the Vitamin A, 99% of the Vitamin C and 97% of the Vitamin E remained in the :25 composition.
SChemical Name wt/wt Water JPius Water 53.45% Disodiurn EDTA 0.10% Glycerin 5.00% Phenoxyethanol 0.73% Methyl paraben 0.3 Propyl paraben 0.17% Hydroxyethylcellulose 0.30% Xanthan Gum 0.50% Butylhydroxytoluene 0.10% Octyl methoxycinnamate 7.50% Avobenzone 3.00% Glycey Monostearate PEG- 100 5.00% Octyl Hydroxstearate 2.00% Wey Alcohol 2.00% C12-C15 Alkyli Benzoate 5.00% Ps dm Ascorbic Acid 2.00% i a 24- Tocopherol 1.00% Retinol 0.25% Lactoferrin; thioxanthine; uric acid 1.00% n-acetyl cysteine 0.0 1% Cyriomethicone 1.500/ NaOH Of course, the foregoing examples are merely illustrative of the compositions and *10 methods of this invention and do not represent its full scope.
Claims (18)
1. Compositions containing oil-soluble and/or water-soluble oxygen-labile species comprising oil-soluble or water-soluble oxygen-labile species and one or more stabilizer s 5 compounds selected from the group consisting of: a) thio-containing compounds; and S* b) glycoproteins.
2. Compositions according to claim 1 wherein said thio-containing compounds are selected from the group consisting of sulfites, metabisulfites, glutathione and cysteine derivatives.
3. Compositions according to claim 1 wherein said glycoprotein is lactoferrin.
4. Compositions according to claim 3 wherein said composition further comprises thioxanthine and uric acd.
5. Compositions according to claim 1 wherein said oil-soluble oxygen-labile species are selected from one or more of the group consisting of retinoids, choleciferol, vitamin K tocotrienol, fatty acids, and tocopherol and their derivatives.
6. Compositions according to claim 1 wherein said water-soluble oxygen-labile species are selected from one or more of the group consisting of ascorbic acid and its derviatives, niacin, thiamine, riboflavin, folic acid, pyrodoxine, pantothenic acid, niacinamide, lipoic acid, dihydrolipoic acid, amino acids and their derivatives.
7. A composition according to claim 2 wherein said thio-containing compound is N- acetylcysteine.
8. Compositions according to claim 1 wherein said composition comprises one or more retinoids and one or more tocopherols and one or more ascorbic acid or its 2 5 derivatives.
9. Compositions according to claim 1 wherein said composition comprises ascorbic acid and tocopherol or their derivatives.
Compositions according to claim 1 wherein said composition comprises retinoids and ascorbic acid or its derivatives. 4 .r 1 26
11. Compositions according to claim 1 wherein said composition comprises rednoids.
12. Compositions according to claim 1 wherein said composition comprises ascorbic acid or its derivatives.
13. Compositions according to claim 1 wherein said composition comprises s tocopherol or its derivatives.
14. Compositions according to claim 8 wherein said compositions comprise lactoferrin or iniferine.
15. Compositions according to claim 8 wherein said compositions comprise N-acetyl cysteine.
16. A method of stabilizing compositions containing oil-soluble or water-soluble oxygen-labile species or combinations thereof comprising adding to said compositions oil- soluble or water-soluble oxygen-labile species one or more stabilizer compounds selected from the group consisting of: S. a) thio-containing compounds; and is b) glycoproteins.
17. A composition containing oil-soluble and/or water-soluble oxygen-labile species substantially as herein described with reference to any one of the embodiments of the invention illustrated in the examples.
18. A method of preparing a composition containing oil-soluble and/or water-soluble oxygen-labile species substantially as herein described with reference to any one of the embodiments of the invention illustrated in the examples. DATED this 29th Day of May, 2000 JOHNSON JOHNSON CONSUMER COMPANIES, INC. Attorney: DENIS ENG TUFFERY Registered Patent Attorney of BALDWIN SHELSTON WATERS
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13644299P | 1999-05-28 | 1999-05-28 | |
US60/136442 | 1999-05-28 | ||
US36142599A | 1999-07-27 | 1999-07-27 | |
US09/361425 | 1999-07-27 |
Publications (2)
Publication Number | Publication Date |
---|---|
AU3780000A true AU3780000A (en) | 2001-02-22 |
AU767784B2 AU767784B2 (en) | 2003-11-27 |
Family
ID=26834307
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
AU37800/00A Ceased AU767784B2 (en) | 1999-05-28 | 2000-05-29 | Compositions for stabilizing oxygen-labile species |
Country Status (11)
Country | Link |
---|---|
US (2) | US20020123460A1 (en) |
EP (1) | EP1055720B1 (en) |
JP (1) | JP2001011441A (en) |
KR (1) | KR20010049430A (en) |
CN (1) | CN1182832C (en) |
AT (1) | ATE273364T1 (en) |
AU (1) | AU767784B2 (en) |
CA (1) | CA2309520A1 (en) |
DE (1) | DE60012820T2 (en) |
ES (1) | ES2230030T3 (en) |
IN (1) | IN2000KO00299A (en) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10062401A1 (en) * | 2000-12-14 | 2002-06-20 | Beiersdorf Ag | Use of folic acid and / or derivatives thereof for the preparation of cosmetic or dermatological preparations for the prophylaxis of damage to the skin's own DNA and / or to repair damage already occurred to the skin's own DNA |
US6955816B2 (en) * | 2001-11-16 | 2005-10-18 | Klysz Beatrice M | Anti-aging skin care composition and uses thereof |
AU2003904192A0 (en) * | 2003-08-11 | 2003-08-21 | Adelaide Research and Innovaiton Pty Ltd | Method for inhibiting bacterial colonisation |
US20050048012A1 (en) * | 2003-08-26 | 2005-03-03 | Roland Jermann | Use of biotin or a biotin derivative for skin lightening purposes and for the treatment of senile lentigines |
CA2536204A1 (en) * | 2003-09-10 | 2005-03-24 | The Procter & Gamble Company | Skin care composition |
DE102004003478A1 (en) * | 2004-01-22 | 2005-08-18 | Basf Ag | Retinoid-containing preparations |
FR2887149B1 (en) * | 2005-06-17 | 2007-08-03 | Galderma Sa | PROCESS FOR SOLUBILIZING THE METRONIDAZOLE |
DE102004046063A1 (en) * | 2004-09-22 | 2006-03-23 | Henkel Kgaa | Hair treatment agent, useful to decrease olfactory absorption in keratinic fibers, comprises apolar components and protein-complex trace elements of e.g. zinc, magnesium, potassium or ferrous |
JP4545632B2 (en) * | 2005-04-25 | 2010-09-15 | 株式会社 伊藤園 | Folic acid-containing composition and method for stabilizing folic acid |
CA2623725A1 (en) * | 2005-09-30 | 2007-04-12 | Omp, Inc. | Stable ascorbic acid compositions |
US8840883B2 (en) | 2007-12-06 | 2014-09-23 | Naidu Lp | Metallo-protein and tocotrienol (MP-T3) compositions with non-protein-type metal chelator and uses thereof |
US8309080B2 (en) * | 2007-12-06 | 2012-11-13 | Naidu Lp | Metallo-protein and tocotrienol (MP-T3) compositions and uses thereof |
JP5351174B2 (en) * | 2007-12-31 | 2013-11-27 | コヴィディエン リミテッド パートナーシップ | Disinfectant composition, method and system |
JP5179950B2 (en) * | 2008-05-26 | 2013-04-10 | 雪印メグミルク株式会社 | Folic acid and / or vitamin B12-lactoferrin complex |
IT1403089B1 (en) * | 2010-11-18 | 2013-10-04 | Polimeri Europa Spa | STABILIZED COMPOSITION INCLUDING ETHYLENE HOMOPOLYMERS OR COPOLYMERS AND NATURAL ANTIOXIDANTS |
FR2968955B1 (en) * | 2010-12-15 | 2012-12-28 | Oreal | COSMETIC COMPOSITION COMPRISING ASCORBIC ACID |
JP2013079216A (en) | 2011-10-04 | 2013-05-02 | Snow Brand Milk Products Co Ltd | Sense-improving agent |
JP6287342B2 (en) * | 2014-03-03 | 2018-03-07 | ライオン株式会社 | Dentifrice composition and method for improving stability of ascorbic acid phosphate ester or salt thereof in dentifrice composition |
JP2018503689A (en) * | 2015-01-27 | 2018-02-08 | フローレンゲイル・エル・エル・シー | Healing topical composition |
IT201700006360A1 (en) * | 2017-01-20 | 2018-07-20 | Italdevice Srl | Composition for ophthalmic use |
JP2018150265A (en) * | 2017-03-13 | 2018-09-27 | 株式会社ミルボン | Cleansing composition and cleansing product |
Family Cites Families (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS537488B2 (en) * | 1972-12-28 | 1978-03-18 | ||
DD150694A1 (en) * | 1980-04-16 | 1981-09-16 | Gisela Raether | METHOD FOR STABILIZING PHARMACEUTICAL PREPARATES WITH OXIDATING SENSITIVITIES |
JPS57112367A (en) * | 1980-12-29 | 1982-07-13 | Sankyo Co Ltd | Preparation of stable aqueous solution of compound having thiol group |
FR2641696B2 (en) * | 1986-04-11 | 1991-03-08 | Sederma Sa | USE OF A MIXTURE CONTAINING LACTOFERRIN IN FREE ANTI-RADICAL COSMETIC PREPARATIONS |
FR2596986B1 (en) * | 1986-04-11 | 1988-09-23 | Sederma Sa | USE OF LACTOFERRIN IN COSMETIC, FREE ANTIRADICAL PREPARATIONS |
JPH0645587B2 (en) * | 1986-11-04 | 1994-06-15 | 富士写真フイルム株式会社 | Sulfinic acid compound and antioxidant composition containing the same |
FR2610626B1 (en) * | 1987-02-09 | 1989-05-19 | Oreal | NOVEL ANTI-OXIDIZER SYSTEM BASED ON A STABILIZED ASCORBYL ESTER, COMPRISING AT LEAST ONE COMPLEXING AGENT AND AT LEAST ONE THIOL, AND COMPOSITIONS CONTAINING SUCH ANTI-OXIDIZING SYSTEM |
JP2799568B2 (en) * | 1988-04-06 | 1998-09-17 | 株式会社コーセー | Antioxidant composition |
DE3814806A1 (en) * | 1988-05-02 | 1989-11-16 | Christoph V Dr Rer Nat Stein | Method for the stabilisation of amino-acid infusion solutions |
DE3822096A1 (en) * | 1988-06-30 | 1990-01-04 | Klinge Co Chem Pharm Fab | STABILIZED DRUG PREPARATION |
GB9002422D0 (en) * | 1990-02-03 | 1990-04-04 | Boots Co Plc | Anti-microbial compositions |
WO1993000085A1 (en) * | 1991-06-27 | 1993-01-07 | Johnson And Johnson Consumer Products, Inc. | Stabilized retinoid-containing skin care compositions |
US5843481A (en) * | 1994-01-18 | 1998-12-01 | Mount Sinai Hospital Corporation | Treatment of proliferative disorders, metastasaes, and drug resistant tumors with vanadate compounds and derivatives or analogues thereof |
FR2721208B1 (en) * | 1994-06-16 | 1996-08-02 | Oreal | Composition for topical use containing an antioxidant and a bacterial extract, and use of this composition. |
JP3681200B2 (en) * | 1994-09-07 | 2005-08-10 | ジョンソン・エンド・ジョンソン株式会社 | Container for skin care composition |
US6461622B2 (en) * | 1994-09-07 | 2002-10-08 | Johnson & Johnson Consumer Companies, Inc. | Topical compositions |
JP3810821B2 (en) * | 1994-12-26 | 2006-08-16 | 森永乳業株式会社 | Peptide derivatives and their uses |
US5614173A (en) * | 1995-12-08 | 1997-03-25 | Isp Investments Inc. | Hair spray composition having 80% or less VOC and advantageous physical and performance characteristics |
WO1997021423A1 (en) * | 1995-12-11 | 1997-06-19 | The Procter & Gamble Company | Topical retinoid composition |
JPH09176679A (en) * | 1995-12-26 | 1997-07-08 | Okawa Shokuhin Kogyo Kk | Method of rendering powdery unsaturated fatty acid antioxidant, antioxidant composition of powdery unsaturated fatty acid, and functional food |
JP3511546B2 (en) * | 1996-02-02 | 2004-03-29 | 雪印乳業株式会社 | Iron-enriched edible fats and oils |
DE19609477A1 (en) * | 1996-03-11 | 1997-09-18 | Basf Ag | Stable aqueous solubilisates of carotenoids and vitamins |
US5744148A (en) * | 1996-09-20 | 1998-04-28 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Stabilization of an unstable retinoid in oil-in-water emulsions for skin care compositions |
JPH10236975A (en) * | 1997-02-21 | 1998-09-08 | Morinaga Milk Ind Co Ltd | Antioxidative composition |
TWI234467B (en) * | 1997-06-04 | 2005-06-21 | Univ Michigan | Composition for inhibiting photoaging of skin |
FR2768623B1 (en) * | 1997-09-22 | 1999-12-31 | Jean Noel Thorel | COSMETIC AND / OR DERMATOLOGICAL COMPOSITION FOR TOPICAL USE FOR THE TREATMENT OF OILY SKIN |
JP4100750B2 (en) * | 1998-02-13 | 2008-06-11 | 株式会社Adeka | Emulsified oil and fat composition |
-
2000
- 2000-05-24 IN IN299KO2000 patent/IN2000KO00299A/en unknown
- 2000-05-25 CA CA002309520A patent/CA2309520A1/en not_active Abandoned
- 2000-05-26 ES ES00304519T patent/ES2230030T3/en not_active Expired - Lifetime
- 2000-05-26 DE DE60012820T patent/DE60012820T2/en not_active Expired - Lifetime
- 2000-05-26 AT AT00304519T patent/ATE273364T1/en not_active IP Right Cessation
- 2000-05-26 KR KR1020000028686A patent/KR20010049430A/en not_active Application Discontinuation
- 2000-05-26 EP EP00304519A patent/EP1055720B1/en not_active Expired - Lifetime
- 2000-05-29 CN CNB00118833XA patent/CN1182832C/en not_active Expired - Fee Related
- 2000-05-29 JP JP2000158635A patent/JP2001011441A/en active Pending
- 2000-05-29 AU AU37800/00A patent/AU767784B2/en not_active Ceased
-
2001
- 2001-12-27 US US10/033,492 patent/US20020123460A1/en not_active Abandoned
-
2004
- 2004-05-28 US US10/856,440 patent/US20040242463A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1055720A3 (en) | 2001-03-07 |
AU767784B2 (en) | 2003-11-27 |
EP1055720A2 (en) | 2000-11-29 |
DE60012820T2 (en) | 2005-09-01 |
ES2230030T3 (en) | 2005-05-01 |
KR20010049430A (en) | 2001-06-15 |
CN1182832C (en) | 2005-01-05 |
IN2000KO00299A (en) | 2005-11-18 |
CN1284327A (en) | 2001-02-21 |
US20020123460A1 (en) | 2002-09-05 |
CA2309520A1 (en) | 2000-11-28 |
EP1055720B1 (en) | 2004-08-11 |
DE60012820D1 (en) | 2004-09-16 |
US20040242463A1 (en) | 2004-12-02 |
JP2001011441A (en) | 2001-01-16 |
ATE273364T1 (en) | 2004-08-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU767784B2 (en) | Compositions for stabilizing oxygen-labile species | |
US6641845B1 (en) | Skin whitening composition comprising bearberry and tetrahydrocurcumin | |
EP0885000B1 (en) | Topical compositions comprising an oil-in-water emulsion and a retinoid | |
US6080393A (en) | Skin care composition comprising a retinoid | |
US5023235A (en) | Antioxidant system based on an ascorbyl ester in combination with a complexing agent and a thiol and to compositions containing the same | |
US6193956B1 (en) | Topical compositions | |
US5976555A (en) | Topical oil-in-water emulsions containing retinoids | |
EP1108419B1 (en) | Cosmetic composition and methods of use | |
KR100819173B1 (en) | Cosmetic compostion comprising vitamin c | |
WO1996007396A9 (en) | Retinoid compositions | |
US20080206170A1 (en) | Creatine compositions for skin treatment | |
WO2000000162A1 (en) | Skin whitening composition | |
WO2003086329A2 (en) | Skincare compositions comprising anti-oxidant agents | |
EP1383478A2 (en) | Skin composition | |
US20090232757A1 (en) | Use of gamma-amino butyric acid as a depigmenting agent | |
JPH027287B2 (en) | ||
JPS61215318A (en) | External agent for skin | |
JPH07101844A (en) | Multilayered emulsion | |
US20020193349A1 (en) | Stabilizer for l-ascorbic acid-2-sodium phosphate | |
JPS60188306A (en) | Cosmetic | |
JP4889069B2 (en) | Moisturizer, whitening agent and skin cosmetics | |
JPH0753647B2 (en) | Liquid transparent skin cosmetics | |
JP2000016928A (en) | Antiperspirant | |
JPH11292749A (en) | Preparation for external use for skin | |
CH703818A2 (en) | Agent, useful e.g. useful as a skin brightening agent, sunscreens, deodorants and soaps and for bleaching age and pigment spots, comprises a disulfide compound or its acid addition salt |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FGA | Letters patent sealed or granted (standard patent) |